Phase 1-2 Vatalanib and Gemcitabine in Advanced Pancreatic Cancer

Inclusion criteria

• Histologically or cytologically confirmed adenocarcinoma of the pancreas
• Unresectable (due to involvement of critical vasculature, adjacent organ invasion, or presence of metastasis)
• If > 5 years between the primary surgery and the development of metastatic disease, then separate histological or cytological confirmation of metastatic disease
• Primary or metastatic lesion within 4 weeks prior to entry of study
• WHO performance status of 0 to 2
• ≤ 18 years of age
• Absolute Neutrophil Count (ANC) ≥ 1.5 x 10e9/L (>= 1500/mm3)
• Platelets (PLT) ≥ 100 x 10^9/L (≥ 100,000/mm3)
• Hemoglobin (Hgb) ≥ 9 g/dL
• Serum creatinine ≤ 1.5 upper limit of normal (ULN)
• Serum bilirubin ≤ 1.5 ULN
• Aspartate aminotransferase (AST/SGOT) and alanine aminotransferase

• (ALT/SGPT) ≤ 3.0 x ULN OR
• ≤ 5 x ULN if liver metastases present
• Proteinuria:

• Negative for proteinuria based on dip stick reading OR
• If dip stick reading is +1 result, then total urinary protein ≤ 500 mg and measured creatinine clearance (CrCl) ≥ 50 mL/min from a 24-hour urine collection
• Life expectancy ≥ 12 weeks
• Ability to give written informed consent

Exclusion criteria

• For the "phase 1" portion of the study: prior gemcitabine will be therapy.
• For the "phase 2" portion of the study: any prior chemotherapy {except for low-dose 5-fluorouracil (5-FU)as a radiosensitizer]
• Radiotherapy (RT). The site of previous RT must have progressive disease if the only site of disease).

• Prior full field radiotherapy ≤ 4 weeks prior to enrollment OR
• Limited field radiotherapy ≤ 2 weeks prior to enrollment. Patients must have recovered from all therapy-related toxicities.
• Prior biologic or immunotherapy ≤ 2 weeks prior to registration.
• Prior therapy with anti-VEGF agents
• History or presence of central nervous system (CNS) disease
• Patients with a history of another primary malignancy ≤ 5 years (Exception: inactive basal or squamous cell carcinoma of the skin)
• Major surgery ≤ 4 weeks prior to enrollment. (Exception: insertion of a vascular access device)
• Minor surgery ≤ 2 weeks prior to enrollment. (Exception: insertion of a vascular access device)
• Concurrent use of other investigational agents and patients who have received investigational drugs ≤ 4 weeks prior to enrollment.
• Pregnant, or breast-feeding, not employing an effective method of birth control.
• Pre-existing peripheral sensory neuropathy with functional impairment (≥ CTCAE grade 2 neuropathy)
• Respiratory compromise due to pleural effusion or ascites (≥ CTCAE grade 2 dyspnea)
• QTc > 450 ms (male) or > 470 ms (female)
• Uncontrolled high blood pressure
• History of labile hypertension
• History of poor compliance with an antihypertensive regimen
• Unstable angina pectoris
• Symptomatic congestive heart failure
• Myocardial infarction ≤ 6 months prior to registration / randomization
• Serious uncontrolled cardiac arrhythmia
• Uncontrolled diabetes
• Active or uncontrolled infection
• Interstitial pneumonia
• Extensive and symptomatic interstitial fibrosis of the lung
• Chronic renal disease
• Acute or chronic liver disease
• Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of vatalanib
• Human immunodeficiency virus (HIV) infection (confirmed), if there is potential for interaction between vatalanib and any anti-HIV medication
• HIV infection (confirmed) judged to increase subject risk due to the pharmacologic activity of vatalanib
• Receiving warfarin sodium (Coumadin) or similar. Heparin is allowed.
• Unwilling to or unable to comply with